About this Research Topic
The growing incidence of multidrug-resistant (MDR), extensively-drug resistant (XDR), and totally-drug resistant (TDR) pathogens is one of the biggest challenges facing modern medicine. These pathogens have been recognized by CDC, as serious threats to human health, with mortality rates in invasive infections due to MDR and XDR pathogens exceeding 50% in some cases. The growing prevalence of pathogens resistant to most or even all currently available antimicrobial agents heralds the potential risk of a future “post-antibiotic era”.
In recent years, both treatment and prophylaxis pipelines are based mainly on existing drug classes and their analogs. Therefore, vastly reduced therapeutic armamentarium stands as a major challenge in clinical practice and refers to infections caused by fungal agents, Mycobacteria, as well as Gram-positive and Gram-negative pathogens. As a result, the increased emergence of MDR, XDR, PDR or TDR pathogens considerably reduces the opportunities for effective treatments against infections resulting from these pathogens.
The majority of antimicrobial compounds implemented in recent years derived from mesophilic soil microorganisms, however this source seems to be exhausted, hence the need for new strategies to search for active compounds. Novel promising molecules that could potentially overcome existing resistance involve (i) membranes biosynthetic pathway; (ii) cell wall biosynthetic pathway, and (iii) targeting transport machinery. However, seeking for novel targets within pathogens’ cell would be of highest importance, especially in the context of possible broadening the spectrum of structurally and functionally novel compounds. Additionally, there is another promising approach based on antivirulence therapeutics potentially acting as (i) antitoxins, (ii) quorum sensing disruptors, (iii) virulence regulatory systems silencers, and (iv) factors interfering with bacterial adherence and biofilm formation processes.
Meanwhile, combination therapy based on drugs currently available can often be an effective approach, enabling to overcome existing resistance mechanisms and minimizing the phenomenon of further selection of drug-resistant subpopulations.
With this Research Topic, we welcome contributions on the emerging antimicrobials against drug-resistant pathogens, targeting: their sources, specific mechanisms of action, possible spectrum of activity, available combination antimicrobial therapy, and mechanisms of resistance.
This Research Topic is intended to compose a collection of high-quality Original Research articles, Reviews, Mini-Reviews, and Perspective articles that cover, but are not limited to, the following themes:
● novel compounds against M. tuberculosis
● novel agents and combination antimicrobial therapy against:
○ drug-resistant Enterobacterales and non-fermenters
○ drug-resistant Staphylococcus spp. and Enterococcus spp.
● antifungals against MDR pathogens such as, C. auris, Trichophyton mentagropytes/interdigitale Complex,
Emergomyces spp., Mucormycosis, etc.
● investigation of novel target sites based on microorganism–antimicrobial interactions determined on
phenotypic and molecular level
● combination antimicrobial therapy with possible synergistic applications
● molecular mechanisms of resistance against novel antimicrobials
● characterization of mobile genetic elements (MGEs) involved in dissemination of factors involved in adaptive
resistance
● description of bacterial regulatory mechanisms involved in adaptive resistance against novel antimicrobials
● molecular epidemiology of pathogens resistant to emerging antimicrobials
In recent years, both treatment and prophylaxis pipelines are based mainly on existing drug classes and their analogs. Therefore, vastly reduced therapeutic armamentarium stands as a major challenge in clinical practice and refers to infections caused by fungal agents, Mycobacteria, as well as Gram-positive and Gram-negative pathogens. As a result, the increased emergence of MDR, XDR, PDR or TDR pathogens considerably reduces the opportunities for effective treatments against infections resulting from these pathogens.
The majority of antimicrobial compounds implemented in recent years derived from mesophilic soil microorganisms, however this source seems to be exhausted, hence the need for new strategies to search for active compounds. Novel promising molecules that could potentially overcome existing resistance involve (i) membranes biosynthetic pathway; (ii) cell wall biosynthetic pathway, and (iii) targeting transport machinery. However, seeking for novel targets within pathogens’ cell would be of highest importance, especially in the context of possible broadening the spectrum of structurally and functionally novel compounds. Additionally, there is another promising approach based on antivirulence therapeutics potentially acting as (i) antitoxins, (ii) quorum sensing disruptors, (iii) virulence regulatory systems silencers, and (iv) factors interfering with bacterial adherence and biofilm formation processes.
Meanwhile, combination therapy based on drugs currently available can often be an effective approach, enabling to overcome existing resistance mechanisms and minimizing the phenomenon of further selection of drug-resistant subpopulations.
With this Research Topic, we welcome contributions on the emerging antimicrobials against drug-resistant pathogens, targeting: their sources, specific mechanisms of action, possible spectrum of activity, available combination antimicrobial therapy, and mechanisms of resistance.
This Research Topic is intended to compose a collection of high-quality Original Research articles, Reviews, Mini-Reviews, and Perspective articles that cover, but are not limited to, the following themes:
● novel compounds against M. tuberculosis
● novel agents and combination antimicrobial therapy against:
○ drug-resistant Enterobacterales and non-fermenters
○ drug-resistant Staphylococcus spp. and Enterococcus spp.
● antifungals against MDR pathogens such as, C. auris, Trichophyton mentagropytes/interdigitale Complex,
Emergomyces spp., Mucormycosis, etc.
● investigation of novel target sites based on microorganism–antimicrobial interactions determined on
phenotypic and molecular level
● combination antimicrobial therapy with possible synergistic applications
● molecular mechanisms of resistance against novel antimicrobials
● characterization of mobile genetic elements (MGEs) involved in dissemination of factors involved in adaptive
resistance
● description of bacterial regulatory mechanisms involved in adaptive resistance against novel antimicrobials
● molecular epidemiology of pathogens resistant to emerging antimicrobials
Keywords: multidrug-resistance, pandrug-resitance, acquired resistance mechanism, Candida auris, Trichophyton mentagropytes, Trichophyton interdigitale, Emergomyces sp, Mucormycosis, total-drug resistance, novel antimicrobials
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